Pulmonary cryptococcosis in a ruxolitinib-treated patient with primary myelofibrosis

Abstract

We present the case of a 79-year-old man who showed multiple pulmonary nodules on chest computed tomography (CT) after being treated for 6 months with ruxolitinib, an inhibitor of Janus kinase (JAK) 1 and 2, to treat primary myelofibrosis. We examined the lesions by bronchoscopy, and the biopsy specimen revealed fungus bodies of Cryptococcus with granulomatous inflammation. As a result, the patient was diagnosed with pulmonary cryptococcosis. The patient was treated with fluconazole (200 mg daily for 2 weeks) with concomitant ruxolitinib administration, but the pulmonary lesions progressed. Subsequently, the patient was treated with voriconazole (300 mg daily for 3 weeks), but the lesions worsened further. The administration of ruxolitinib was therefore discontinued, and the dosage of voriconazole was increased to 400 mg daily. Three months later, the pulmonary lesions diminished in size. The present case of pulmonary cryptococcosis occurred in a patient treated with ruxolitinib. Treatment of pulmonary cryptococcosis with concomitant JAK inhibitor administration may result in poor treatment efficacy. It might be better to stop administration of JAK inhibitors, if possible, in patients being treated for pulmonary cryptococcosis.

Ruxolitinib‐associated infections: A systematic review and meta‐analysis

“…Eight papers were excluded for the following reasons: pooled analysis ( n = 1), follow‐up of phase I or II trial ( n = 1), sub‐analyses ( n = 2), data on extension phase study with a shorter follow‐up ( n = 2), redundant publications ( n = 2). Five phase III RCTs (3 phase IIIa with their most recently published extended phase (750 patients) and 2 phase IIIb RCTs (283 patients)), 6 phase IV studies (1524 patients) and 28 case report publications (31 patients, of whom 4 were included also in phase III studies and 1 in phase IV study) were included in this systematic review.…”

A case report of disseminated histoplasmosis and concurrent cryptococcal meningitis in a patient treated with ruxolitinib

“…This case draws attention to three key factors. The first is the degree of immunosuppression seen with ruxolitinib and the increasing number of reported fungal cases associated with the drug [5–8]. The second, which was noted on initial phase III trials of ruxolitinib, but must be emphasized, is that the adverse effects from immunosuppression may occur at various intervals after the initiation of ruxolitinib.…”

“…The phase 3 study of ruxolitinib (COMFORT II trial) [4] reported that reactivation of herpes zoster virus and tuberculosis were the predominant infections seen with ruxolitinib, as well as a trend towards higher rates of bacterial infections. Since that time, case reports have emerged, documenting the development of Pneumocystis jiroveci pneumonitis, toxoplasmosis retinitis, progressive multifocal leukoencephalopathy (PML), as well as cryptococcal meningoencephalitis and pulmonary cryptococcus in patients treated with ruxolitinib [5–9].…”

IFN-γ immune priming of macrophages in vivo induces prolonged STAT1 binding and protection against Cryptococcus neoformans

“…neoformans [ 16 , 17 , 19 – 22 , 26 ]. To date, myelofibrosis treatment of two patients with Ruxolitinib, which inhibits JAK1,2 and likely STAT1, is hypothesized to have contributed to the development of cryptococcosis in these individuals [ 27 , 28 ].…”